Category:
Basic Sciences/Biologics; Ankle
Introduction/Purpose:
One of the most common procedures for treating end-stage osteoarthritis of the foot and ankle is arthrodesis 1. However, a significant ...complication with arthrodesis is the development of non-union. Thus, identification of adjuvants to enhance osteogenesis are paramount to fusion success. One possible molecule is the immunosuppressant FK506 (Tacrolimus). Previous research 2 demonstrated FK506 as a stand-alone small molecule capable of initiating osteogenesis and bone formation. The purpose of this study was to evaluate the osteogenic potential of FK506 alone and in combination with other bioactive factors to provide a foundation for future in vivo and clinical applications.
Methods:
Marrow-derived cells (MDCs) were isolated from juvenile bovine femoral condyles, to represent cells present at the ankle fusion site. MDCs (P1) were seeded at 50k cells per well (24-well plate). After 14 days, the wells were stained for calcium deposits using Alizarin Red S, and imaged with brightfield microscopy to visualize calcium deposits. Drug combinations of potentially osteogenic small molecules were tested (simvastatin, platelet derived growth factor PDGF, tamoxifen, triiodothyronine). The highest alizarin red absorbance values were used to choose the best drug combination. These combinations were further evaluated for gene expression by RT-qPCR Osteocalcin (OCN), Osteopontin (OPN), and Bone Sialoprotein (IBSP). To simulate a 3D osteogenic environment, cells were seeded into fibrin gels (to mimic the “fusion clot”), cultured for 14 days, and sectioned/stained with Alizarin red.
Results:
FK506 and PDGF produced the highest level of calcium staining compared to other bioactive factors, highlighted via heatmap of alizarin red absorbance values (Figure 1A). Compared to the control, FK506, PDGF, and the combination of both all resulted in enhanced alizarin red staining (Figure 1A/B). Overall, FK506 exhibited an increased expression across all genes. PDGF and the combination of FK506 and PDGF had a more varied expression within the genes queried (Figure 1C). Finally, in a fibrin gel system, variability was observed between gels of the same group. Displaying the best, middle, and worst sections give a comprehensive view of the explained variability. Across the sections, the FK506-PDGF combination showed the densest mineralization, highlighted by the dark maroon regions of the section (Figure 1D).
Conclusion:
This study confirms that FK506 demonstrates osteogenesis within marrow-derived cells (representative of a fusion site). The combination of FK506 to PDGF may enhance PDGF’s known healing potential within arthrodesis applications. This work provides the foundation for future clinical applications of FK506. Ongoing studies are focused on the effect of FK506, and potentially in combination with PDGF, in an rabbit ankle fusion model to evaluate efficacy and bone formation.
The authors thank the American Orthopaedic Foot and Ankle Society (AOFAS) and Emory Department of Orthopaedics for their support and funding.
References: 1 Park 2022. 2 Sangadala 2019
Objectives
To determine whether a home‐based multicomponent physical activity counseling (PAC) intervention is effective in reducing glycemic measures in older outpatients with prediabetes mellitus.
...Design
Controlled clinical trial.
Setting
Primary care clinics of the Durham Veterans Affairs (VA) Medical Center between September 29, 2008, and March 25, 2010.
Participants
Three hundred two overweight (body mass index 25–45 kg/m2), older (60–89) outpatients with impaired glucose tolerance (fasting blood glucose 100–125 mg/dL, glycosylated hemoglobin (HbA1c) <7%) randomly assigned to a PAC intervention group (n = 180) or a usual care control group (n = 122).
Intervention
A 12‐month, home‐based multicomponent PAC program including one in‐person baseline counseling session, regular telephone counseling, physician endorsement in clinic with monthly automated encouragement, and customized mailed materials. All study participants, including controls, received a consultation in a VA weight management program.
Measurements
The primary outcome was a homeostasis model assessment of insulin resistance (HOMA‐IR), calculated from fasting insulin and glucose levels at baseline and 3 and 12 months. HbA1c was the secondary indicator of glycemic control. Other secondary outcomes were anthropometric measures and self‐reported physical activity, health‐related quality of life, and physical function.
Results
There were no significant differences between the PAC and control groups over time for any of the glycemic indicators. Both groups had small declines over time of approximately 6% in fasting blood glucose (P < .001), and other glycemic indicators remained stable. The declines in glucose were not sufficient to affect the change in HOMA‐IR scores due to fluctuations in insulin over time. Endurance physical activity increased significantly in the PAC group (P < .001) and not in the usual care group.
Conclusion
Home‐based telephone counseling increased physical activity levels but was insufficient to improve glycemic indicators in older outpatients with prediabetes mellitus.
This study was conducted to examine the association between ideal cardiovascular health (CVH) and health-related quality of life and health status indicators.
This cross-sectional study included ...adult NHANES participants from 2001 to 2010 without CVD (N = 7115). CVH was defined according to AHA definitions with poor, intermediate and ideal levels of the seven factors (diet, BMI, physical activity, smoking, blood pressure, glucose, and cholesterol) assigned scores of 0, 1, and 2, respectively. A CVH score (CVHS) was calculated as the sum of the scores from each individual health factor (range 0-14; higher score indicating greater CVH). CVHS was categorized as poor (0-7), intermediate (8-10), and ideal (11-14). Linear regression models examined the association between CVHS category with health status and number of unhealthy days per month, adjusted for socio-demographic characteristics and disability.
Among US adults 20-79 years, 14, 46 and 40% had ideal, intermediate and poor CVHS, respectively. Compared to those with poor CVH, individuals in intermediate and ideal CVH were 44 and 71% less likely to report being in fair/poor health. Participants with ideal CVH scores reported a mean of 2.4 fewer unhealthy days over the past month, including one less day in which their physical health was not good and two fewer days in which their mental health was not good.
Ideal CVH is associated with greater overall health status and fewer physically and mentally unhealthy days.
Smoking is a poor prognostic factor for healing after rotator cuff repair and is associated with inferior results. We hypothesized that smokers would have higher recurrent tear rates and more ...postoperative myotendinous junction (MTJ) retraction in healed repairs than nonsmokers three months postoperatively.
Rotator cuff repairs (RCRs) were retrospectively reviewed over a 2-year period. Patients underwent magnetic resonance imaging (MRI) within 6 months prior to surgery and again at 3 months postoperatively. Seventy-nine patients were included and stratified by smokers versus nonsmokers. Baseline patient demographics, tear characteristics, and surgical factors were collected. Preoperative and postoperative MRIs were assessed to quantify the MTJ position and to establish the recurrent tear rate.
For the total cohort (nonsmokers, n = 56; smokers, n = 23), significant differences in age, race, and traumatic onset of injury existed between groups. There were no significant differences in recurrent tear between smokers (26%) and nonsmokers (27%), but nonsmokers were more satisfied. For patients with healed RCRs (nonsmokers, n = 41; smokers, n = 17), there were significant differences in race. On univariate analysis, nonsmokers had a significantly more lateral MTJ postoperatively (P = 0.05). On multivariable regression analysis, medialized postoperative MTJ position in healed cuffs was driven only by greater preoperative rotator cuff retraction preoperatively. There were no significant differences in MTJ position based on smoking status for patients with healed RCRs.
Smoking does not appear to be an independent risk factor for postoperative MTJ retraction in healed RCRs, also known as failure in continuity. Preoperative tear size and retraction play the biggest roles in predicting postoperative MTJ position, regardless of smoking status. There are no significant differences in patient-reported outcomes for patients with healed RCRs, but nonsmokers had more satisfaction following RCR in the total cohort.
Level III; Retrospective cohort study; Diagnostic study
Abstract
Background
The introduction of universal masking policies at many American healthcare institutions during the COVID-19 pandemic represented a major shift in infection prevention protocol. ...However, despite their widespread use, previous data on face masks as a tool for preventing respiratory infections before COVID have been mixed, frequently showing no benefit. This study examines the impact of a universal face mask policy on rates of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), community-acquired pneumonia (CAP), and other non-COVID pneumonias of indeterminate etiology at Ascension Borgess Hospital in Kalamazoo, Michigan.
Methods
An analytical cross-sectional study was performed comparing patient data from March through September 2019 with the same period in 2020 for any patient admitted with any ICD-10 code for pneumonia. Chi-square analysis was employed to determine pneumonia frequency by subtype, pre and post-mandate. A significance level of p < 0.05 was used for all tests.
Results
1187 patient records were collected, 28 were excluded for incompleteness, and 1159 were included in our analysis. The study population was 81.80% White and 53.66% male. 670 patients (57.81%) were pre-mask mandate and 487 (42.19%) were post-mandate. Pre-mandate, 107 patients had HAP, 575 had all-cause pneumonia (non-COVID pneumonia of any etiology), and 0 had VAP. Post-mandate, 84 patients had HAP, 2 had VAP, and 376 had all-cause pneumonia. A significant difference was observed in the number of all-cause pneumonia cases between pre and post-mandate (χ2 = 13.3058, p < 0.0001), but not in HAP cases (χ2 = 0.2996, p = 0.5841). There were only two instances of VAP; therefore, inferential statistics were not obtained.A significant difference was observed in all-cause pneumonia cases between pre and post-mask mandate implementation (χ2 = 13.3058, p <0.0001), but not in HAP cases (χ2 = 0.2996, p = 0.5841).
Conclusion
Among hospitalized patients, a significant difference in HAP pre and post-mandate was not observed. However, the incidence of non-COVID pneumonia of any etiology was significantly lower during the mask mandate (p < 0.0001). Wether this difference is attributable to universal masking or other mandated or non-mandated precautionary behaviors in the hospital or community cannot be determined. These results suggest that mask mandates as currently implemented do not prevent HAP, but may play a role in decreasing total pneumonia prevalence in the community.
Disclosures
All Authors: No reported disclosures
This study shows that the strategies of service firms affect the uncertainty they encounter in their dealings with customers. This strategically induced uncertainty then becomes the mechanism by ...which service firms organize their production processes. In a study of 234 service firms representing 96 different industries, we found strong support for relationships between these organizations' strategies and the level of complexity in their production processes. In addition, service firms that possessed the hypothesized fit between strategy and service production complexity tended to experience higher performance.
One-electron oxidation of the β-diketiminate titanium(III) bis-neopentyl complex (Nacnac)Ti(CH2 t Bu)2 (Nacnac = ArNC(Me)CHC(Me)NAr, Ar = 2,6-(CHMe2)2C6H3) promotes α-abstraction to afford the rare ...and terminal four-coordinate neopentylidene (Nacnac)TiCH t Bu(OTf), which was structurally characterized. Alkylidene (Nacnac)TiCH t Bu(OTf) reacts cleanly with benzophenone and the imine functionality of the Nacnac ligand to afford the corresponding Wittig-type products.
Stroke is a severe and prevalent syndrome for which there is a great need for treatment, including agents to block the cascade of brain injury that occurs in the hours after the onset of ischemia. ...Reactive oxygen species (ROS) have been implicated in this destructive process, but antioxidant enzymes such as superoxide dismutase (SOD) have been unsatisfactory in experimental stroke models. This study is an evaluation of the effectiveness of salen-manganese complexes, a class of synthetic SOD/catalase mimetics, in a rat focal ischemia model involving middle cerebral artery occlusion. We focus on EUK-134, a newly reported salen-manganese complex demonstrated here to have greater catalase and cytoprotective activities and equivalent SOD activity compared with the previously described prototype EUK-8. The administration of EUK-134 at 3 hr after middle cerebral artery occlusion significantly reduced brain infarct size, with the highest dose apparently preventing further infarct growth. EUK-8 was also protective but substantially less effective. These findings support a key role for ROS in the cascade of brain injury after stroke, even well after the onset of ischemia. The enhanced activity of EUK-134 suggests that, in particular, hydrogen peroxide contributes significantly to this injury. Overall, this study suggests that synthetic SOD/catalase mimetics might serve as novel, multifunctional therapeutic agents for stroke.
Until now, micrometeorological measurements of surface/ atmosphere exchange fluxes of submicron aerosol chemical components such as nitrate, sulfate or organics could only be made with gradient ...techniques. This article describes a novel setup to measure speciated aerosol fluxes by the more direct eddy covariance technique. The system is based on the Aerodyne quadrupole-based Aerosol Mass Spectrometer (Q-AMS), providing a quantitative measurement of aerosol constituents of environmental concern at a time resolution sufficient for eddy-covariance. The Q-AMS control software was modified to maximize duty cycle and statistics and enable fast data acquisition, synchronized with that of an ultrasonic anemometer. The detection limit of the Q-AMS based system for flux measurements ranges from 0.2 for NO
3
−
to 15 ng m
−2
s
−1
for hydrocarbon-like organic aerosol (HOA), with an estimated precision of around 6 ng m
−2
s
−1
, depending on aerosol loading. At common ambient concentrations the system is capable of resolving deposition velocity values < 1 mm s
−1
, sufficient for measurements of dry deposition to vegetation. First tests of the system in the urban environment (6 to 20 June 2003) in Boulder, CO, USA, reveal clear diurnal, presumably traffic related, patterns in the emission of HOA and NO
3
−
, with indication of fast production of moderately oxygenated organic aerosol below the measurement height, averaging about 15% of the HOA emission. The average emission factor for HOA was 0.5 g (kg fuel)
−1
, similar to those found in previous studies. For NO
3
−
an emission factor of 0.09 g (kg fuel)
−1
was estimated, implying oxidation of 0.5% of the traffic derived NO
x
below the measurement height of 45 m. By contrast, SO
4
2−
fluxes were on average downward, with deposition velocities that increase with friction velocity from 0.4 to 4 mm s
−1
.
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